HOX Gene Expression in Phenotypic and Genotypic Subgroups and Low HOXA Gene Expression as an Adverse Prognostic Factor in Pediatric ALL
Abstract
RNA expression of HOXA7-10, HOXA13, and HOXB2-4 genes was exclusively detected in leukemic cells and immature progenitors. RNA expression of HOXB6 and CDX2 genes was exclusively detected in leukemic cells but not in B-lineage cells.
HOXA3-4, HOXA7, and HOXB3-4 genes were differentially expressed between BCP-ALL and T-ALL subgroups, and among genotypically defined MLL/AF4, TEL/AML1, BCR/ABL, hyperdiploid and normal karyotype subgroups. However, this differential expression did not define specific clusters in hierarchical cluster analysis.
HOXA7 gene was low expressed at the RNA level in patients with hyperdiploid leukemia, whereas wHOXB7 and CDX2 genes were low expressed in TEL/AML1-positive and BCR/ABL-positive cases, respectively. In contrast, in acute myeloid leukemia, high HOXA RNA expression was associated with an excellent prognosis in Cox's regression model (P = 0.03).
In MLL/AF4-positive ALL, lower HOXA RNA expression correlated with the methylation status of their promoters.